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Biomedical subjects

L S Chan

Publications and source records attributed to L S Chan.

At least 127 records · Page 7Linked to original sources
PubMed1990

Interleukin-1 in human skin: dysregulation in psoriasis.

Cytokine dysregulation is an attractive concept to explain many of the observed abnormalities in psoriasis. IL-1, in particular, can potentiate immune cellular activation, activate fibroblasts, and increase endothelial cell adhesiveness to leukocytes. Here, we review IL-1 regulation in normal and psoriatic skin in vivo in relation to normal skin and cultured keratinocytes. Contrary to expectations, IL-1 functional activity in psoriatic lesions is reduced, not increased, relative to normal skin. The reduction is attributable to the presence of IL-1 inhibitors, reduced IL-1alpha levels, and an IL-1beta that lacked function in T-cell assays. IL-1beta protein is actually significantly increased in psoriatic lesions, but the mechanism of its non-functionality remains unclear. Unlike cultured keratinocytes, which accumulate large, inactive IL-1beta precursors, both normal and psoriatic skin process IL-1beta to a mature form. Novel mechanisms of post-translational processing by epidermis in vivo may generate a novel form of IL-1beta with unknown functions. The marked abnormalities of IL-1 regulation in psoriatic skin suggest that this molecule may be important in normal skin homeostasis.

Humans↗
PubMed1989

Expression and function of the UM4D4 antigen in human thymus.

UM4D4 is a newly identified T cell surface molecule, distinct from the Ag receptor and CD2, which is expressed on 25% of peripheral blood T cells, resting or activated. Monoclonal anti-UM4D4 is mitogenic for T cells and T cell clones. Since alternative activation pathways independent of Ag/MHC recognition may be important in thymic differentiation, the expression and function of UM4D4 was examined in human thymus. UM4D4 was found on the surface of 6% of thymocytes. All thymocyte subsets contained UM4D4+ cells but expression was greatest on thymocytes that were CD1- (12%), CD3+ (11%) and especially CD4-CD8- (18%). CD3+CD4- CD8- cells, most of which bear the gamma delta-receptor, were greater than or equal to 50% + for UM4D4. Moreover, anti-UM4D4 was comitogenic for thymocytes together with PMA or IL-2. Anti-UM4D4 also reacted strongly with a subset of thymic epithelial cells in both cortex and medulla. Dual color fluorescence microscopy, with anti-UM4D4 and antibodies to other thymic epithelial Ag, showed UM4D4 expression on neuroendocrine thymic epithelium but not on thymic fibrous stroma. Thus, UM4D4 is expressed on, and represents an activation pathway for, a subset of thymic T cells. In addition, this determinant, initially identified as a novel T cell activating molecule, is broadly expressed by neuroendocrine thymic epithelium. Although the function of UM4D4 on the thymic epithelial cells is not yet clear, it is possible that UM4D4 represents a pathway for the functional activation of a subset of the thymic epithelium as well as a subset of thymocytes, thus playing a dual role in T cell differentiation.

Antibodies, Monoclonal↗
PubMed1989

Underutilization of antihypertensive drugs and associated hospitalization.

The association of underutilization of drugs prescribed for the treatment of hypertension and acute-care hospital readmissions was evaluated. The data base consisted of computerized hospitalization records and computerized out-patient pharmacy records, checked by chart audit for validity. The number of days' supply of antihypertensive agents was estimated by dividing the quantity of drugs dispensed by the daily dose indicated by the prescription instructions. All patients had been admitted to an acute-care hospital during a 6-month period with the diagnosis of hypertension. Following discharge from the hospital, drug utilization and readmission status were determined for a minimum of 1 year. The drug compliance of a group of patients who were readmitted to the hospital was compared with the patients who were not readmitted. The readmitted group had a significantly higher ratio of days when they were without any antihypertensive agents relative to the length of time in the study. There were no statistically significant differences in demographic features or blood-pressure levels between the patient groups. These findings indicate that underutilization of antihypertensive drugs may be associated with hospitalization, which could be prevented if patients had complied with their medication schedules.

Adult↗
PubMed1989

Activation of Mg-ATPase of skeletal-muscle myosin by bovine retinal pigment epithelial actin.

The morphology and function of actin in cultured bovine retinal pigment epithelial (RPE) cells were studied. Filamentous actin was identified with a fluorescent mushroom toxin, nitrobenzoxadiazole (NBD)-phallacidin, specific for actin. Dark-field microscopy of cultured RPE cells revealed numerous pigment granules; fluorescent microscopy identified scattered lipofuscin granules. One-dimensional SDS polyacrylamide gel electrophoresis of urea-soluble proteins extracted from RPE cells showed a 46,000-dalton protein band which comigrated with authentic muscle actin. Densitometric scanning showed that this protein band comprised 7.6% of the total urea-soluble proteins. An actin-activated skeletal-muscle myosin Mg-ATPase assay, using skeletal-muscle heavy meromyosin as enzyme and [gamma-32P]-ATP as substrate, demonstrated functional actin in RPE cell extracts after DEAE-cellulose anion exchange chromatography. The actin-containing protein fractions were eluted at ionic strengths between 0.19 and 0.36 M KCl. The activation of myosin ATPase by actin in RPE cells provides a molecular basis for the phagocytic activity which is important in maintaining the integrity of retinal photoreceptor cells.

Actins↗
PubMed1989

What happens to babies exposed to phencyclidine (PCP) in utero?

Fifty-seven infants exposed to phencyclidine (PCP) in utero were followed for the first year of life. Thirty-six (65%) of the 55 for whom birth records were available manifested symptoms of neonatal narcotic withdrawal syndrome, including 16 (52%) of those whose mothers denied opiate abuse during pregnancy. Temperament problems were noted in 47% of the babies and sleep problems in 14%. The majority of infants grew normally, but a larger than expected number started out small and remained small. Testing using the Bayley Scales of Infant Development at age one year revealed a mental development index (mean +/- SD) of 94 +/- 10 and a psychomotor development index of 98 +/- 10. Attachment behavior was abnormal in 17%. Most infants were cared for by their natural mother. Further studies are needed to determine later effects of in utero PCP exposure, as well as effects on the infants being raised by women who have used PCP. Phencyclidine toxicity needs to be considered when evaluating babies with signs of neonatal narcotic withdrawal syndrome.

Birth Weight↗
PubMed1989

Beta-cluster haplotypes, alpha-gene status, and hematological data from SS, SC, and S-beta-thalassemia patients in southern California.

The beta-gene-cluster haplotype and alpha-gene status were determined for 221 patients with sickle cell anemia, 41 with SC disease, and 21 with S-beta-thalassemia. Among SS patients, eleven beta S haplotypes were found in 21 combinations. Three haplotypes--the Benin (Ben) [---+-], the Central African Republic (CAR) [+---+], and the Senegal (Sen) [+- ]--comprise 61%, 21%, and 10% of the chromosomes, respectively. Cleavage at the Xmn I site 5' to the G gamma gene was observed only when the Senegalese arrangement was present. The linear correlation which exists between the absolute value of the G gamma chains and the Hb F for each haplotype combination suggests a feed-back mechanism which controls the G gamma to A gamma ratio and thus the Hb F level (or vice versa). The A gamma T chain was present with specific haplotypes [++-++] and [++-+-]. Heterozygous or homozygous alpha-thalassemia-2 was present in 36% of the SS patients and was randomly distributed among beta S-gene-cluster haplotypes. The variable levels of hemoglobin, MCV, Hb F, G gamma chains, and Hb A2 are in response to the heterogeneous genetic mix of the beta S-gene-cluster haplotypes and alpha-thalassemia-2 in American patients with sickle cell anemia. The influence of alpha-thalassemia-2 on the level of Hb F is dependent on the beta S-cluster haplotype. Hb A2 levels increased with decrease in the number of alpha genes. Among SC and S-beta-thalassemia patients the beta-cluster polymorphisms on the beta S chromosome were those commonly associated with the African origins of beta S haplotype. The haplotype [+--+-] was present on the C chromosome in 90% of the cases. Most beta-thalassemia chromosomes had haplotypes that matched the common African polymorphisms. An alpha-gene deletion was found in 29% of the SC and S-beta-thalassemia patients.

Adolescent↗
PubMed1989

Epidermolysis bullosa acquisita in childhood. Differentiation from hereditary epidermolysis bullosa.

Epidermolysis bullosa acquisita (EBA), rarely reported in childhood, is described in a 10-year-old black girl. The age of onset during infancy and the clinical appearance mimicked hereditary dystrophic epidermolysis bullosa. Epidermolysis bullosa acquisita was diagnosed by direct immunofluorescence of perilesional skin, indirect immunofluorescence on normal epithelium and saline-split skin, direct immunoelectron microscopy, and immunoblotting of the patient's serum sample against partially purified EBA antigen/carboxyl domain of type VII collagen. Differentiation of mechanobullous disease in children is critical in that significant clinical benefit may be achieved in EBA with prednisone and/or dapsone therapy. A search for associated immunologic abnormalities and HLA-DR typing may help our understanding of EBA.

Age Factors↗
PubMed1989

Comparison of neonatal mortality rates between transports to tertiary and intermediate neonatal intensive care units.

The differential of neonatal mortality rates between infant transports to tertiary and to intermediate neonatal intensive care units (NICUs) was examined based on 8,391 one-time infant transports from community hospitals to tertiary or intermediate NICUs in Southern California in the three-year period 1981-1983. Among the demographic, birth and delivery, and diagnostic characteristics studied, nine were identified to be related significantly to the higher neonatal mortality rate among transports to tertiary NICUs: birthweight, gestational age, necessity of intubation, multiple clinical conditions, presence of cardiac, neurologic, and genitourinary problems, anomalies, and syndromes. Adjusting for differences in the number of cases with necessity of intubation and the presence of the five clinical problems reduced the neonatal mortality ratio of tertiary to intermediate NICUs from 1:56 to 1:01, while adjustment for birthweight and gestational age differences reduced the ratio from 1.56 to 1.54. This analysis indicates that the difference of neonatal mortality between the two levels of NICUs can be explained to a larger extent by the higher proportion of infants requiring intubation with serious clinical problems. Birthweight and gestational age played only a minor role in this respect.

Apgar Score↗
PubMed1989

Coexistence of pemphigus vulgaris and progressive localized scleroderma.

In this article, we describe a patient with progressive localized scleroderma, who subsequently developed pemphigus vulgaris on the previously affected sclerodermatous skin, and on the oral mucosa, the nasal mucosa, the laryngeal mucosa, and the scalp. The coexistence of pemphigus vulgaris with localized scleroderma and the histopathologic documentation of pemphigus vulgaris arising on a sclerodermatous skin have not been previously reported. Whether this is a random association or an association based on common immunologic pathomechanisms in pemphigus and localized scleroderma may be important in understanding these diseases.

Adult↗
PubMed1988

Effect of human corneal fibroblasts on lymphocyte proliferation in vitro.

Cocultivation of human corneal fibroblasts (CFB) with allogeneic peripheral blood mononuclear cells (PBL) induced a minimal lymphocyte proliferative response, even when the fibroblasts had been pre-treated with interferon-gamma (IFN-gamma) and were HLA-DR positive. IFN-gamma-treated CFB did not express detectable HLA-DQ alloantigens. Cocultivation of CFB with PBL in the presence of Concanavalin A (Con A) or Phytohemagglutinin inhibited mitogen-induced lymphocyte proliferation by 40-90% relative to PBL cultured without CFB. Induction of HLA-DR expression on the CFB did not alter their inhibitory properties. Addition of indomethacin to cultures reversed the effect of CFB on Con A responses. However, no difference between proliferative responses to HLA-DR positive or negative CFB was seen in the presence of indomethacin. This weak response to induced Class II alloantigens on CFB suggests that induction of Class II alloantigens on corneal stroma alone may be insufficient to sensitize a recipient for Class II alloantigen-driven corneal graft rejection.

Antibodies, Monoclonal↗
PubMed1988

Predictors of short-term prognosis in patients with pulmonary tuberculosis.

We evaluated 191 consecutive adults with pulmonary tuberculosis in order to develop methods to determine which patients should be initially hospitalized. Using stepwise discriminant analysis, we found the six factors that were most strongly associated with an unfavorable short-term outcome (respiratory failure or death): lymphopenia, advanced age, concomitant smear-positive extrapulmonary tuberculosis, alcoholism, a high percentage of neutrophils on the differential white blood cell count, and lack of radiographic evidence of cavitation. We derived a scoring system incorporating these variables and separated patients into high- and low-risk groups. The system was prospectively validated by applying it to a separate group of 179 patients. Lymphocyte-transformation tests in 32 patients revealed an association between clinical markers of poor prognosis and minimal lymphocyte proliferation to a heat-killed strain of Mycobacterium tuberculosis.

Adolescent↗
PubMed1987

The course of fever during treatment of pulmonary tuberculosis.

We studied 161 patients with pulmonary tuberculosis: 55 (34%) were afebrile and 106 (66%) were febrile at presentation. Febrile patients were younger and more symptomatic than afebrile individuals. Fever was also associated with a higher incidence of lymphopenia, hyponatraemia, hypoalbuminaemia and many acid-fast bacilli on sputum smear. Most patients were treated with isoniazid, rifampicin and pyrazinamide. Of 83 individuals who became afebrile while in hospital, 74 (89%) did so within a week and 77 (93%) in 2 weeks. Prolonged fever was associated with alcoholism, anaemia, hyponatraemia and hypoalbuminaemia. A therapeutic trial of antituberculosis drugs may be more useful than has been previously thought, since in most patients the temperature falls to normal within 2 weeks.

Adult↗
PubMed1987

Age and dose interval as factors in agglutinin formation to pertussis vaccine.

The agglutinin response to pertussis agglutinogens in diphtheria-tetanus-pertussis (DTP) vaccine was determined in human infants inoculated initially at ages four weeks to eight months. The effects of age at the time of initial dose and the interval between subsequent doses were specifically evaluated. Our findings demonstrate that optimum agglutinin production is best achieved with DTP vaccine by beginning immunization at five months of age or later followed by a second dose at eight weeks or more. Variation in the two variables, age and dose interval, decreases the likelihood of an optimum agglutinin response.

Age Factors↗
PubMed1987

Is sickle cell crisis a valid measure of clinical severity in sickle cell anemia?

We studied the conditional probability of developing a sickle cell crisis in 509 patients with sickle cell anemia (SS), with variable number of prior crises. These SS patients were followed during different calendar eras, having diverse complications, and had entered and/or lost to follow-up at different ages. The probability of having a sickle cell crisis during the first three decades of life increases significantly with the number of prior crises episodes (p less than 0.001). After more than five cryptogenic crises, the patient has developed a patterned response to stress that overshadows other influences, such as the effects of therapeutic agents, thus lessening the 'power' of sickle crisis as a measure of morbidity.

Age Factors↗
PubMed1986

Hypokalemia in thiazide-treated systemic hypertension.

Potassium supplementation in diuretic-induced hypokalemia (serum potassium less than 3.5 mmol/liter) in patients being treated for hypertension is a common event. In a previous study 40 mmol/day of orally administered potassium was not effective in preventing diuretic-induced hypokalemia in patients who had previously developed hypokalemia while being treated for hypertension with hydrochlorothiazide. In the study reported here dosages as high as 60 to 80 mmol/day of orally administered potassium failed to prevent hypokalemia in 7 of 19 hypertensive patients who were receiving hydrochlorothiazide. Potassium supplementation was compared with the potassium-sparing diuretic amiloride. The study design was open label and subject matched with crossover of therapeutic regimens.

Aldosterone↗
PubMed1986

Non-competitive inhibition of myo-inositol transport in cultured bovine retinal capillary pericytes by glucose and reversal by Sorbinil.

myo-Inositol transport by retinal capillary pericytes in culture was characterized. The major myo-inositol transport process was sodium-dependent, ouabain-sensitive, and saturable at 40 mM, indicating a carrier-mediated process. The sodium ion concentration required to produce one-half the maximal rate of myo-inositol uptake ([Na+]0.5) did not show dependence on the external myo-inositol concentration (22.3 mM sodium for 0.005 mM myo-inositol; 18.2 mM sodium for 0.05 mM myo-inositol). myo-Inositol transport was an energy-dependent, active process functioning against a myo-inositol concentration gradient. The kinetics of the sodium-dependent system fitted a 'velocity type' co-transport model where binding of sodium ion to the carrier increased the velocity (Vmax 28 to 313 pmol myo-inositol/micrograms DNA per 20 min when [Na+] varied from 9 to 150 mM) but not the affinity for myo-inositol (Km 0.92 to 0.83 mM when [Na+] varied from 9 to 150 mM). Metabolizable hexoses (D-glucose or D-galactose; greater than 5 mM) inhibited myo-inositol uptake. Dixon-plot analysis indicated that the inhibition was non-competitive with a Ki of 22.7 mM for D-glucose and 72.6 mM for D-galactose. The inhibition was significantly reversed by Sorbinil (0.1 mM), an aldose reductase inhibitor. In contrast, high concentrations of non-metabolizable hexoses (L-glucose, 3-O-methyl-D-glucose), or partially metabolizable 2-deoxy-D-glucose, did not significantly inhibit myo-inositol uptake. The inhibitory effect of D-glucose or D-galactose on myo-inositol transport appeared to be related to glucose or galactose metabolism via the polyol pathway.

3-O-Methylglucose↗
PubMed1986

Actin in cultured bovine retinal capillary pericytes: morphological and functional correlation.

Actin in cultured bovine retinal capillary pericytes was identified and partially characterized biochemically. The filamentous actin was localized in bovine retinal capillary pericytes using a fluorescent mushroom toxin (nitrobenzoxadiazole-phallacidin) specific for actin. One-dimensional SDS-polyacrylamide-gel electrophoresis of urea-extracted proteins from bovine retinal capillary pericytes revealed a 46,000 MW protein band corresponding to an actin standard, which comprised 7.3% of the total urea-soluble proteins. Actin-activated skeletal muscle myosin Mg2+-ATPase assay, using [gamma-32P]-ATP as substrate, demonstrated functional actin in bovine retinal capillary pericyte extracts after DEAE-cellulose anion-exchange chromatography. The actin-containing protein fractions were eluted at ionic strengths between 0.25 and 0.35 M KCl. The presence of functional actin in pericytes indicated the ability to generate contractile force. This contraction-generating ability may allow pericytes to regulate microvessel caliber and to maintain the integrity of the capillary wall. A lack of this function when pericytes are preferentially lost in diabetic retinal microangiopathy could destabilize the microvessel wall and predispose the capillary to further pathologic changes.

Actins↗